Our investigations will explore factors affecting patients' responses to drugs. The effects of environment disease states, concomitant drug administration and hormonal state, will continue to be evaluated. Although the major thrust will be toward human studies, in patients where feasible, animal and in vitro models will be used where needed. New techniques will be developed to quantitate drug levels, metabolite distribution and concentration and drug effects, both beneficial and deleterious, in an attempt to improve rational drug therapy. Correlations between drug and metabolite levels and drug action will be sought. Biliary function, gastrointestinal, cardiovascular and neuropsychiatric clinical pharmacology will continue to be the major areas of study.